The central tenet of this proposal is that the Dlx family of homeobox genes is essential for regulating the differentiation and function of forebrain GABAergic neurons. Accordingly, I suggest that the Dlx genes are required for controlling the development, and perhaps the function, of intemeurons in the cerebral cortex, and projection neurons in the basal ganglia. Therefore, understanding the functions of the Dlx genes should yield insights into the roles of GABAergic neurons in forebrain neural systems, and may provide insights into disorders of the forebrain due to defects in GABAergic neurons. The experiments described herein use standard and conditional genetic methods to alter the expression of the Dlx genes in developing mice. These methods will allow us to study the effects of deleting individual and/or multiple Dlx genes on the development and function of forebrain GABAergic neurons. In addition, we will investigate the effects of ectopically expressing the Dlx genes. These studies have implications for understanding the genetic pathways that regulate the specification, differentiation and function of forebrain GABAergic neurons, and have implications for understanding the molecular bases of human disorders of GABAergic neurotransmission.